All species on the planet, including humans, are exposed to 24-hour patterns of light and darkness as the Earth rotates on its axis. In response to these natural light-dark patterns, species have evolved biological rhythms known as circadian rhythms that repeat approximately every 24 hours. Examples of circadian rhythms include oscillation in core body temperature, hormone secretion, sleep, and alertness. Circadian oscillations occur at the cellular level, including cell mitosis and DNA repair. In mammals, the central circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the brain's hypothalamus. This master clock provides timing cues throughout the body to regulate the diverse physiological, hormonal and behavioral circadian rhythms. The timing of the circadian pacemaker in humans is slightly longer than 24 hours, so the exogenous light-dark pattern (i.e. natural light-dark pattern caused by the Earth's rotation) resets the timing of the SCN every day as seasons change or as we travel. In this way, our internal clock can be synchronized with the local solar time anywhere on the planet. A breakdown in the synchrony between the circadian pacemaker and the local solar time (as can occur with travel), will disrupt sleep, digestion, alertness, and in chronic cases, research suggests may cause cardiovascular anomalies and/or accelerated cancerous tumor growth.
As an example, epidemiological studies have shown that rotating-shift nurses, who experience a marked lack of synchrony between rest-activity patterns and light-dark cycles, are at higher risk for breast cancer compared with day-shift nurses. More specifically, environmental factors such as electric light at night (LAN) have been implicated as agents in endocrine disruption. It is hypothesized that LAN suppresses pineal melatonin production by the pineal gland, which may shift rest-activity patterns, making them asynchronous with the solar day/night cycle. It has also been shown that melatonin is an antioxidant, significantly retarding the growth of breast cancer and other tumors. In fact, it probably plays a significant role in the development of cancer in mammals. Moreover, in addition to heightened cancer risks, other diseases have been associated with night-shift work, such as diabetes and obesity, which suggests a role of circadian disruption in the development and progression of such diseases.
Though many environmental stimuli have been reported to influence the central circadian pacemaker in mammals, light is established as the dominant environmental stimulus that synchronizes, or entrains, the circadian pacemaker to the local environment, e.g. the light-dark cycle. Furthermore, it is known that light must be incident on the retina to be a stimulus for the human circadian pacemaker. In 2002, a new photoreceptor in the retina was discovered, the intrinsically photosensitive retinal ganglion cell, which has direct nerve projections to the circadian pacemaker in the SCN. This discovery solidified the importance of light in affecting the circadian pacemaker and has invigorated research into light therapy for treating health issues thought to originate from circadian disruption.
The human circadian pacemaker continues to oscillate in the absence of environmental stimuli, but with a free running period slightly different than 24 hrs. In humans, the average free running period is approximately 24.2 hrs. Depending on when light is applied over the course of 24 hrs, it can advance, delay, or have very little effect on the phase of an individual's circadian pacemaker. For instance, light applied before the body reaches its minimum core body temperature will delay the phase of the pacemaker while light applied after the body reaches its minimum core body temperature will advance the phase of the circadian pacemaker. Since the human circadian pacemaker is, on average, slightly longer than 24 hrs, humans generally need morning light to maintain synchronization (or entrainment) between the circadian pacemaker and the local time.
A mathematical model was developed by Kronauer and others that predicts the effect of light on the human circadian pacemaker. The human circadian pacemaker may be modeled as a Van der Pol type limit-cycle oscillator with a nonlinear light dependent driving force. Simulating the behavior of the circadian pacemaker for various light input patterns can be done by numerically solving the set of differential equations that describe the oscillator.
The phase of the circadian pacemaker rhythm may be assessed, in one aspect, by measuring the concentration of proteins that participate in circadian rhythm regulation. For humans, certain hormones related to circadian rhythm such as melatonin, cortisol, alpha amyloid, have also been used as circadian rhythm markers. These types of direct measurements are intrusive in terms of measurements (blood serum, saliva) and time consuming and expensive in terms of analysis. As a result, the sampling rate is very low, at best once per several hours, over limited duration during experimental trials. Much more desirable is the use of indirect markers, such as body temperature, heart/pulse rate, activity level, etc. However, these type of markers or biological signals are “masked” by other factors, e.g., light stimulates activity response via visual pathway in addition to the circadian pathway, environmental conditions could affect body temperature as well as heart rate, etc. There are numerous methods that estimate circadian phase based on measured biomarkers. Most of these methods are batch-based, meaning that the circadian rhythm is extracted in post-processing after the signal has been completely obtained. For instance, the techniques may include the manual inspection of actogram, statistical method, Fourier analysis, cosinor, and activity onset.